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Abstract

Department of Public Health and Primary Care, Institute of Public Health, University
of Cambridge, Cambridge, UK.BACKGROUND: Results of experimental and clinical studies
suggest that insulin-like growth factor-I (IGF-I) and IGF binding protein-1 (IGFBP-1)
could be important determinants of glucose homoeostasis. However, experimental models
might also reflect compensatory and adaptive metabolic processes. We therefore prospectively
examined the associations between circulating concentrations of IGF-I and IGFBP-1
and development of glucose tolerance. METHODS: Participants in this cohort study were
a random sample of 615 normoglycaemic men and women aged 45-65 years. Participants
underwent oral glucose tolerance testing based on WHO definitions and criteria in
1990-92 and 1994-96. At the baseline visit, we measured serum concentrations of IGF-I
and IGFBP-1, and assessed the relation between these peptides and subsequent glucose
intolerance. FINDINGS: At 4.5 years of follow-up, 51 (8%) of 615 participants developed
impaired glucose tolerance or type-2 diabetes. After adjustment for correlates of
IGF-I and risk factors for glucose intolerance, the odds ratio for risk of impaired
glucose tolerance or type-2 diabetes for participants with IGF-I concentrations above
the median (> or = 152 microg/L) compared with those with concentrations below the
median (<152 microg/L) was 0.50 (0.26-0.95). Consistent with this finding, IGF-I also
showed a significant inverse association with subsequent 2-h glucose concentrations,
which was independent of correlates of IGF-I and risk factors for glucose tolerance
(p for linear trend=0.026). We also found that this inverse association was independently
modified by IGFBP-1 (p for interaction=0.011). INTERPRETATION: These data show that
circulating IGF-I and its interaction with IGFBP-1 could be important determinants
of glucose homoeostasis and provide further evidence for the possible protective role
of IGF-I against development of glucose intolerance.PMID: 12049864 [PubMed - indexed
for MEDLINE]